Serum anti-T agglutinins are antibodies having specificity for the cryptic blood group substance known as the Thomsen-Friedenreich T-antigen. The T-antigen has been found in all human sera and in the sera of other mammals such as rabbits and goats. Localized on erythrocytes, T-antigen is considered an immediate biosynthetic precursor of blood group MN antigens, and not expressed under ordinary circumstances. However, MN antigens may be converted in vitro to T-antigen by either an enzymatic or acidic pH treatment [G. F. Springer et al., Carbohydrate Research, 40, 183, (1975)].
A significant level of circulating anti-T agglutinin appears during the first year after birth and by the age of three, it reaches titers found in adult sera [P. E. Lind et al., Australian J. Expl. Biol. Med. Sci., 25, 247, (1947)].
While a normal, healthy adult usually exhibits constant mean anti-T titers, higher than normal titers have been measured in sera from patients exhibiting atypical pneumonia and liver cirrhosis. Also noteworthy is that significantly reduced agglutinin activities were reported in patients undergoing an antibiotic regimen [V. Boccardi et al., Vox Sang, 27, 268, (1974) and K. Fraser, J. Pathological Bacteriology, LXX, 13, (1955)].
Recently, it was observed and reported that anti-T could serve as a useful marker for the diagnosis of carcinoma because depressed levels of anti-T were found in sera from individuals diagnosed as having a malignant disease [Springer et al., Clin. Immunol. Immunopath., 7, 426, (1977)]. In particular, the serum anti-T agglutinin levels were reported to be severely depressed among patients diagnosed to have breast carcinoma or gastrointestinal carcinoma. Those studies detecting a correlation between depressed levels of anti-T and malignant disorders were conducted by a hemagglutination procedure. Specifically, normal human red cells treated with an enzyme (neuraminidase) expose T-antigens on their surface and thereby become T-antigen-bearing red cells. These red cells will agglutinate when anti-T "agglutinating" antibodies are present in the assay system. The degree of agglutination is semi-quantitative in evaluating the antibody levels.
While attempting to duplicate the published results by employing radio-immunoassay techniques, an inconsistency was discovered. Specifically, it was found that the total serum anti-T levels were significantly elevated in samples obtained from untreated cancer patients compared with those of controls secured from normal, healthy individuals and from subjects with benign pathological diseases.
The apparently inconsistent results have been reconciled by recognizing that not all anti-T antibodies are agglutinating antibodies. The non-agglutinating anti-T antibodies would not agglutinate with the T-antigen-bearing red cells and would, therefore, go undetected in the hemagglutination assay medium. The invention disclosed and claimed herein relies on sensitive and specific immunoassays which can detect all the anti-T antibodies, agglutinating and non-agglutinating, to thereby demonstrate that "total" serum anti-T antibody levels are signficantly elevated in cancer patients when compared with "total" anti-T antibody levels observed in normal, healthy donors and patients with benign pathological diseases.